Potential use of procalcitonin as biomarker for bacterial sepsis in patients with or without acute kidney injury

doi:10.1016/j.jiac.2014.12.001

Journal of Infection and Chemotherapy

Volume 21, Issue 4, April 2015, Pages 257-263

https://doi.org/10.1016/j.jiac.2014.12.001 Get rights and content

Abstract

Introduction

There are few investigations regarding the relationships between procalcitonin (PCT) and the acute kidney injury (AKI) in the diagnosis of sepsis. The purpose of this study was to clarify the diagnostic accuracy of the use of PCT levels in patients with or without AKI.

Methods

This study was conducted as a single-center retrospective study. We enrolled 393 patients in whom PCT were measured on admission. We grouped the patients into non-AKI and AKI, and those with AKI were classified according to the RIFLE criteria (Risk, Injury, Failure). The patients in each group were further classified into the sepsis and the non-sepsis group. We subsequently investigated the diagnostic accuracy of the PCT for detecting sepsis in these groups.

Results

The levels of PCT were significantly higher in the sepsis group than in the non-sepsis group among the non-AKI and each AKI patients (p < 0.0001). The diagnostic accuracy of the PCT for detecting sepsis was determined according to a ROC analysis; AUC value was 0.958 in the non-AKI group, in the Risk, Injury and Failure groups were 0.888 and 0.917, 0.857, respectively. AUC value for non-AKI group was significantly different from that of Failure group (p < 0.05).

Conclusions

In Failure AKI patients, the diagnostic accuracy of the PCT level is significantly lower than non-AKI patients. It is therefore suggested that we should be careful in using PCT value to diagnose sepsis in patients with Failure under RIFLE criteria.

Introduction

Sepsis caused by bacteria is the major cause of death in intensive care unit (ICU) patients. Rapid initiation of the correct treatment is crucial important for improving sepsis condition [1], [2]. Additionally, the most recent international sepsis guidelines entitled “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012” recommend early diagnosis and treatment of sepsis to avoid multiple organ failure and other adverse outcomes [3]. In treatment of sepsis antibiotics have already clear benefits, however potential complications from their inappropriate or prolonged using are also well known. Inappropriate or prolonged using of antibiotics lead to multidrug-resistant bacterial strains, allergic reactions, antibiotic-related colitis, and other adverse events [4], [5], [6]. From such situations it is emphasized that the early and accurate detection of sepsis are very important.

Since the definition of systemic inflammatory response syndrome (SIRS) was proposed by the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) in 1991 [7], many clinical trials on sepsis diagnosis and treatment have been conducted. And sepsis was defined when patients met the criteria for SIRS and an infectious source was documented or strongly suspected based on clinical presentation. Blood culture is frequently used as the “gold standard” diagnostic method for sepsis. However, it usually takes 3–7 days to obtain blood culture results and frequently yields low positive results or low sensitivity [8]. Therefore, the general practical medical treatment used for sepsis is based on the doctor's own experience (empiric therapy).

Many trials have identified potential biomarkers. More than 170 biomarkers have been studied for use in evaluation of sepsis [9]. In 1993, procalcitonin (PCT) was first described as a marker elevated in bacterial infections [10]. In infectious conditions, PCT is released from nearly all tissues including lung, liver, kidney, pancreas, spleen, colon, and adipose tissues [11]. Currently, PCT is recognized as one of the suitable markers for diagnosis of sepsis or severe sepsis. In comparison to other markers which have traditionally been reported, PCT gives a high rate of specificity for sepsis diagnosis [12]. However, the concentration of PCT in the human blood is elevated in various conditions, such as in severe trauma, surgical invasive procedures, and critical burn injury, which leads to SIRS. So it is necessary to be aware of false-positive results [13]. In addition, it has been reported that renal function is a major determinant of PCT levels and thus different thresholds should be applied according to renal function impairment [14]. To the best of our knowledge, there are few studies investigating the relationship between PCT and acute kidney injury (AKI). So, the purpose of this study is to clarify the accuracy of diagnosing sepsis using the PCT levels according to AKI severity.

Section snippets

Materials and methods

This is a retrospective study conducted at Fukuoka University Hospital, which is a 915-bed academic center with 34-bed ICU. The ICU has an average admission of about 800 patients per year. The ICU admissions typically include 60% outpatients (including those transferred from the emergency department), 30% transferred from other hospitals, and 10% in-house patients (not including post-operated and newborn patients). The ratio of adult and pediatric (<16 years) patients was 93:7. The study was

Enrolled patients

We have registered 2582 patients from June 2010 to May 2013, and we excluded 2189 according to the exclusion criteria. Thus, a total of 393 patients (225 men and 168 women) were included in this analysis (Fig. 1). The median age of the patients was 65 (53–76) years. Clinical diagnosis of patients is shown in Table 2. The number of sepsis patients is 110 (sepsis, n = 21; severe sepsis, n = 31; septic shock, n = 58). The microbiological examination results in sepsis patients are shown in Table 3.

Discussion

The most common causes of AKI in critically ill patients are sepsis [17]. So it is necessary that we need to diagnose sepsis in AKI patients the fastest way possible. Recently Mehanic et al. [18] reported that the PCT is a reliable marker that contributes to the early diagnosis of invasive bacterial infections and evaluation of their severity and prognosis. However, status of kidney or liver may contribute to PCT clearance from the plasma, and severe dysfunction of these organs could influence

Competing interests

The authors declare that they have no competing interests.

Acknowledgments

We sincerely thank Ms. Kanae Misumi of the Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University for her help in data encoding.

References (26)

J. Garnacho-Montero et al.
Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis
Crit Care Med
(2003)
C. Alberti et al.
Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study
Intensive Care Med
(2002)
R.P. Dellinger et al.
Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock
Crit Care Med
(2012)
J. Chastre et al.
Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial
J Am Med Assoc
(2003)
N. Singh et al.
Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription
Am J Respir Crit Care Med
(2000)
V.L. Yu et al.
Excessive antimicrobial usage causes measurable harm to patients with suspected ventilator-associated pneumonia
Intensive Care Med
(2004)
R.C. Bone et al.
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine
Chest
(1992)
M.S. Rangel-Frausto et al.
The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study
J Am Med Assoc
(1995)
C. Pierrakos et al.
Sepsis biomarkers: a review
Crit Care
(2010)
M. Assicot et al.
High serum procalcitonin concentrations in patients with sepsis and infection
Lancet
(1993)

S.Y. Cho et al.

Biomarkers of sepsis

Infect Chemother

(2014)

I. Herzum et al.

Inflammatory markers in SIRS, sepsis and septic shock

Curr Med Chem

(2008)

M. Christ-Crain et al.

Procalcitonin in bacterial infections – hype, hope, more or less?

Swiss Med Wkly

(2005)

Cited by (35)

Plasma soluble suppression of tumorigenesis 2 measured in the emergency department for diagnosis and outcome prediction of sepsis: A single-center prospective study
2024, Clinica Chimica Acta
The diagnostic and prognostic performance of soluble Suppression of Tumorigenicity 2 (sST2) in suspected septic patients presenting to the Emergency Department (ED) is largely unknown.
Patients were included in this prospective study if there was high suspicion of sepsis. The plasma level of sST2 was measured during initial ED evaluation. Outcomes were the evaluation of (1) sST2 diagnostic performance (alone and in combination with procalcitonin [PCT]), and (2) sST2 ability to predict 30-day and 90-day all-cause mortality.
Among 569 patients included, 481 (84.5 %) had sepsis or septic shock. Plasma sST2 levels were more elevated in septic patients (159 [71–331] vs 50 [31], [32], [33], [34], [35], [36], [37], [38], [39] ng/mL, P < 0.001). The AUC of sST2 for sepsis diagnosis was lower than the AUC of PCT (0.76 vs 0.85, P = 0.03). The best cut-off for sST2 was 61.7 ng/mL, with a sensitivity of 79.9 % and a specificity of 70.6 %. sST2 was able to correctly reclassify septic patients with PCT <0.5 (NRI 28.9 % [P = 0.02]). sST2 level was an independent predictor of 30-day mortality in a model including clinical variables (aHR 2.03 [1.24–3.33], C-index 0.69).
sST2 could be a useful adjunct in diagnosing sepsis and in all-cause mortality prediction.
Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury
2019, Clinica Chimica Acta
Citation Excerpt :
Furthermore, we calculated the area under the curves (AUCs) to compare the accuracy of P-SEP and PCT concentrations for diagnosing sepsis according to AKI severity. We also evaluated the relationships between concentrations of P-SEP or PCT and the severity of illness (organ dysfunction) or AKI, as P-SEP and PCT concentrations are positively correlated with the severity of sepsis [15,25–29] and AKI [14,15]. Continuous variables were reported as medians and interquartile ranges (IQRs), and the two groups were compared using the Wilcoxon signed rank test.
Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI).
We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis.
In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525) and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, p < .001). The optimal cut-off values for diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin.
In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin.
Using procalcitonin to predict acute kidney injury in septic patients: Caveat emptor?
2019, Journal of the Formosan Medical Association
Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection
2018, Medicina Intensiva
Citation Excerpt :
Patients with bacterial co-infection previous to ICU admission, with CKD and AKIN 3 (creatinine levels ≥4 mg/dL) were excluded from the study. Additionally, patients receiving renal replacement therapies (RRT) were excluded due to potential PCT elimination by RRT.8,9,12,19 Patients were considered to have bacterial co-infection when a respiratory bacterial pathogen was identified within the first two days of ICU admission.
Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection.
To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection.
Secondary analysis of a prospective multicentre observational study.
148 Spanish ICUs.
ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60–2.50 mg/dL and Cr ≥ 2.51–3.99 mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr > 4 mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed.
None.
Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60–10.0] ng/mL vs. 0.40 [0.13–1.20] ng/mL, p = 0.002). Weak correlations between Cr/PCT (rho = 0.18) and Urea (U)/PCT (rho = 0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr R² = 0.03 and U R² = 0.018). Similar results were observed during multiple linear regression analysis (Cr R² = 0.046 and U R² = 0.013).
Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection.
Los niveles de procalcitonina (PCT) pueden elevarse en pacientes con disfunción renal aún en ausencia de infección bacteriana.
Determinar la interacción entre los biomarcadores de disfunción renal aguda (AKI) y las concentraciones séricas de PCT en pacientes ingresados en cuidados intensivos (UCI) debido a infección por gripe.
Análisis secundario de un estudio prospectivo, multicéntrico observacional.
Ciento cuarenta y ocho UCI.
Con infección por gripe sin co-infección bacteriana. Se registraron las variables clínicas, de laboratorio y hemodinámicas. El nivel de AKI fue definido como AKI I y II basado en la creatinina (Cr) sérica (> 1,60-2,50 mg/dl y > 2,51-3,99 mg/dl), respectivamente. Pacientes con insuficiencia renal crónica, técnicas de reemplazo renal o Cr >4 mg/dl fueron excluidos. El análisis estadístico se realizó mediante correlación de Spearman y regresión linear simple y múltiple.
Ninguna.
De los 663 pacientes incluidos, 52 (8,2%) y 10 (1,6%) desarrollaron AKI I y II, respectivamente. Pacientes con AKI fueron más añosos, presentaron más comorbilidades y mayor nivel de gravedad. Los niveles de PCT fueron mayores en pacientes con AKI (2,62 [0,60-10,0] ng/ml vs. 0,40 [0,13-1,20] ng/ml; p = 0,002). Se observaron correlaciones débiles entre Cr/PCT (rho = 0,18) y PCT/U (rho = 0,19). La regresión linear simple evidenció una pobre contribución tanto de Cr (R² = 0,03) como de U (R² = 0,018) sobre los niveles de PCT. Resultados similares fueron obtenidos con la regresión linear múltiple para Cr (R² = 0,046) y U (R² = 0,013).
Aunque los valores de PCT pueden estar elevados en pacientes con AKI, altos niveles de PCT no pueden ser explicados por la disfunción renal y podrían ser un signo de alarma de una potencial infección bacteriana.
Diagnostic and Prognostic Roles of C-Reactive Protein, Procalcitonin, and Presepsin in Acute Kidney Injury Patients Initiating Continuous Renal Replacement Therapy
2023, Diagnostics
Liver transaminase enzyme analysis as a predictor of poor maternal outcome in pregnant women with dengue
2023, Indian Journal of Obstetrics and Gynecology Research

View all citing articles on Scopus

View full text

Original articlePotential use of procalcitonin as biomarker for bacterial sepsis in patients with or without acute kidney injury

Abstract

Introduction

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Enrolled patients

Discussion

Competing interests

Acknowledgments

Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis

Crit Care Med

Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study

Intensive Care Med

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock

Crit Care Med

Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial

J Am Med Assoc

Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription

Am J Respir Crit Care Med

Excessive antimicrobial usage causes measurable harm to patients with suspected ventilator-associated pneumonia

Intensive Care Med

Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine

Chest

The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study

J Am Med Assoc

Sepsis biomarkers: a review

Crit Care

High serum procalcitonin concentrations in patients with sepsis and infection

Lancet

Biomarkers of sepsis

Infect Chemother

Inflammatory markers in SIRS, sepsis and septic shock

Curr Med Chem

Procalcitonin in bacterial infections – hype, hope, more or less?

Swiss Med Wkly

Original article
Potential use of procalcitonin as biomarker for bacterial sepsis in patients with or without acute kidney injury